The notion that antibodies provide a specific, safe and rapid means to develop therapeutics is gaining momentum. With the human genome project almost completed, a large number of novel antibody targets are available. Well established methodologies to make monoclonal antibodies (mAbs) are available as well. These methodologies include both in vitro (phage display, yeast display, viral display etc) and in vivo (immunizations of animals with the target antigen followed by classical hybridoma technology) approaches. Therapeutic antibodies can be fully human, humanized or CDR-grafted. It is believed that of these antibodies, fully-human therapeutic antibodies show most promise as they might be less immunogenic and have a long half-life.
Transgenic (Tg) mice carrying human genes encoding antibodies offer a method of making fully human mAbs rapidly. However, one of the main limitations of this approach is that a large number of proteins are highly conserved, both structurally and functionally, between humans and rodents. In the case of conserved proteins, the majority of antibodies raised would be against regions (epitopes) of proteins that are dissimilar between human and mice. Such regions may or may not yield neutralizing, therapeutic grade mAbs.